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Originally published In Press as doi:10.1074/jbc.C000146200 on April 7, 2000

J. Biol. Chem., Vol. 275, Issue 24, 17925-17928, June 16, 2000
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ACCELERATED PUBLICATION
The Caenorhabditis elegans Sex Determination Protein FEM-1 Is a CED-3 Substrate That Associates with CED-4 and Mediates Apoptosis in Mammalian Cells*

Shing-Leng ChanDagger , Karen S. Y. YeeDagger , Karen Mei Ling Tan, and Victor C. Yu§

From the Institute of Molecular and Cell Biology, 30 Medical Dr., Singapore 117609, Republic of Singapore

Sex-specific elimination of cells by apoptosis plays a role in sex determination in Caenorhabditis elegans. Recently, a mammalian pro-apoptotic protein named F1Aalpha has been identified. F1Aalpha shares extensive homology throughout the entire protein with the C. elegans protein, FEM-1, which is essential for achieving all aspects of the male phenotype in the nematode. In this report, the role of FEM-1 in apoptosis was investigated. Overexpression of FEM-1 induces caspase-dependent apoptosis in mammalian cells. FEM-1 is cleaved in vitro by the C. elegans caspase, CED-3, generating an N-terminal cleavage product that corresponds to the minimal effector domain for apoptosis. Furthermore, CED-4 associates with FEM-1 in vitro and in vivo in mammalian cells and potentiates FEM-1-mediated apoptosis. Similarly, Apaf-1, the mammalian homologue of CED-4 was found to associate with F1Aalpha . These data suggest that FEM-1 and F1Aalpha may mediate apoptosis by communicating directly with the core machinery of apoptosis.


* This work was supported by grants from the National Science and Technology Board of Singapore.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger These authors contributed equally to this work.

§ To whom correspondence should be addressed. Tel.: 65-8743740; Fax: 65-7791117; E-mail: mcbyuck@imcb.nus.edu.sg.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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